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High-throughput experimentation (HTE), the miniaturization and parallelization of reactions, is a valuable tool for accelerating diverse compound library generation, optimizing reaction conditions, and enabling data collection for machine learning (ML) applications. When applied to organic synthesis and methodology, HTE still poses various challenges due to the diverse workflows and reagents required, motivating advancements in reaction design, execution, analysis, and data management. To address these limitations, cutting-edge technologies, automation, and artificial intelligence (AI) have been implemented to standardize protocols, enhance reproducibility, and improve efficiency. Additionally, strategies to reduce bias and promote serendipitous discoveries have further strengthened HTE's impact. This review highlights recent advances at every stage of the HTE workflow, including the development of customized workflows, diverse analysis, and improved data management practices for greater accessibility and shareability. Furthermore, we examine the current state of the field, outstanding challenges, and future directions toward transforming HTE into a fully integrated, flexible, and democratized platform that drives innovation in organic synthesis.
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http://dx.doi.org/10.1002/anie.202506588 | DOI Listing |
Mol Genet Genomics
September 2025
Human Phenome Institute, MOE Key Laboratory of Contemporary Anthropology, Zhangjiang Fudan International Innovation Center, Fudan University, 825 Zhangheng Road, Shanghai, 201203, China.
Accurate variant calling is essential for next-generation sequencing (NGS)-based diagnosis of rare diseases, yet most benchmarking studies have focused on standard cell lines or trio-based samples, with limited relevance to sporadic cases. Here, we systematically compared the performance of DeepVariant and GATK HaplotypeCaller in two Chinese cohorts of patients with sporadic epilepsy (EP) and autism spectrum disorder (ASD). DeepVariant exhibited higher precision and sensitivity in detecting single nucleotide variants (SNVs), while GATK showed a distinct advantage in identifying rare variants, which are often key to understanding the genetic basis of rare diseases.
View Article and Find Full Text PDFEur J Cell Biol
August 2025
Institute of Molecular Pharmacology, Medical Faculty, RWTH Aachen University, Wendlingweg 2, Aachen 52074, Germany. Electronic address:
Keratins are the largest and most diverse group of intermediate filament proteins, providing structural integrity and mechanical strength to epithelial cells. Although their assembly as heterodimers is well established, the specific pairing preferences and molecular basis of keratin dimerisation remain largely unknown. Here, we employ a high-throughput computational pipeline that integrates AlphaFold Multimer (AFM) modelling, VoroIF-GNN interaction interface quality assessment, interaction energy calculations and structural comparisons with experimentally solved structures to systematically investigate keratin heterodimerisation and to provide a guideline for further analysis of intermediate filament assembly.
View Article and Find Full Text PDFJ Comput Chem
September 2025
Johnson & Johnson, Beerse, Belgium.
Herein we report the in silico discovery of 13 novel micromolar potent inhibitors of the SARS-CoV-2 NSP13 helicase validated in cellular antiviral and biophysical ThermoFluor assays. The compounds, discovered using a novel fragment-based pharmacophore virtual screening workflow named FragmentScout, enable the advancement of novel antiviral agents. FragmentScout uses publicly accessible structural data of the SARS-CoV-2 NSP13 helicase, which was previously generated at the Diamond LightSource by XChem high-throughput crystallographic fragment screening.
View Article and Find Full Text PDFSpecific protein detection plays a crucial role in biological analysis and clinical diagnostics, serving as an essential tool for disease diagnosis, therapeutic monitoring, and biological research. However, conventional methods such as immunofixation electrophoresis (IFE) and western blotting (WB) suffer from complex workflows, time-consuming operations, and limited quantification capabilities owing to intricate staining and de-staining procedures. In addition, these traditional immunological detection methods require extensive manual handling and specialized expertise, while low levels of automation restrict their applicability to high-throughput or large-scale analysis scenarios.
View Article and Find Full Text PDFAntipyretic analgesics are typical pharmaceutical and personal care products (PPCPs) that are widely used in our daily life because they relieve fever and pain, and have anti-inflammatory and anti-rheumatic properties. These drugs inhibit the synthesis and release of prostaglandins (PGs) in the neurons of the anterior hypothalamus and exert therapeutic effects as a consequence. However, these drugs are relatively commonly misused and abused, often owing to a lack of proper medication guidance.
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